64 l JANUARY JOGC JANVIER 2014
No. 302, January 2014 (Replaces No. 173, February 2006)
SOGC CLINICAL PRACTICE GUIDELINES
Pregnancy Outcomes After
Assisted Human Reproduction
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
This clinical practice guideline has been prepared by
the Genetics Committee, reviewed by the Reproductive
Endocrinology and Infertility Committee and the Family
Physicians Advisory Committee, and approved by the
Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
Nanette Okun, MD, Toronto ON
Sony Sierra, MD, Toronto ON
R . Douglas Wilson (Chair), MD, Calgary AB
Francois Audibert, MD, Montreal QC
Jo-Ann Brock, MD, PhD, Halifax NS
Carla Campagnolo, MSc, CCGC, London ON
June Carroll, MD, Toronto ON
Lola Cartier, MSc, CCGC, Montreal QC
David Chitayat, MD, Toronto ON
Alain Gagnon, MD, Vancouver BC
Jo-Ann Johnson, MD, Calgary AB
Sylvie Langlois, MD, Vancouver BC
Lynn Murphy-Kaulbeck, MD, Moncton NB
W . Kim MacDonald, MD, Halifax NS
Nanette Okun, MD, Toronto ON
Melanie Pastuck, RN, Cochrane AB
Lih Yeen Tan, MD, Toronto ON
Valda Poplak, Toronto ON
Helen Robson, MA, Toronto ON
Disclosure statements have been received from all contributors .
Key Words: Assisted human reproduction, assisted reproductive
technology, pregnancy outcomes, multiple gestation, imprinting,
congenital anomalies, imprinting disorders .
J Obstet Gynaecol Can 2014;36(1):64–83
Objective: To review the effect of assisted human reproduction (AHR)
on perinatal outcomes, to identify areas requiring further research
with regard to birth outcomes and AHR, and to provide guidelines
to optimize obstetrical management and counselling of prospective
Canadian parents .
Outcomes: This document compares perinatal outcomes of different
types of AHR pregnancies with each other and with those of
spontaneously conceived pregnancies . Clinicians will be better
informed about the adverse outcomes that have been documented
in association with AHR, including obstetrical complications,
adverse perinatal outcomes, multiple gestations, structural
congenital abnormalities, chromosomal abnormalities, and
imprinting disorders .
Evidence: Published literature was retrieved through searches
of MEDLINE and the Cochrane Library from January 2005 to
December 2012 using appropriate controlled vocabulary and key
words (assisted reproduction, assisted reproductive technology,
ovulation induction, intracytoplasmic sperm injection, embryo
transfer, and in vitro fertilization) . Results were not restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies; studies of all designs published
in English from January 2005 to December 2012 were reviewed,
and additional publications were identified from the bibliographies
of these articles . Searches were updated on a regular basis and
incorporated in the guideline to August 2013 . Grey (unpublished)
literature was identified through searching the websites of health
technology assessment and health technology assessment-
related agencies, clinical practice guideline collections, clinical trial
registries, and national and international medical specialty societies .
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1) .
01 . There is increasing evidence that infertility or subfertility is an
independent risk factor for obstetrical complications and adverse
perinatal outcomes, even without the addition of assisted human
reproduction . (II-2)
02 . The relative risk for an imprinting phenotype such as Silver-
Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman
syndrome is increased in the assisted reproduction population, but
the actual risk for one of these phenotypes to occur in an assisted
JANUARY JOGC JANVIER 2014 l 65
Pregnancy Outcomes After Assisted Human Reproduction
pregnancy is estimated to be low, at less than 1 in 5000 . The
exact biological etiology for this increased imprinting risk is likely
heterogeneous and requires more research . (II-2)
01 . All men with severe oligozoospermia or azoospermia
(sperm count < 5 million/hpf) should be offered genetic/
clinical counselling, karyotype assessment for chromosomal
abnormalities, and Y-chromosome microdeletion testing prior to in
vitro fertilization with intracytoplasmic sperm injection . (II-2A)
02 . All men with unexplained obstructive azoospermia should be
offered genetic/clinical counselling and genetic testing for cystic
fibrosis prior to in vitro fertilization with intracytoplasmic sperm
injection . (II-2A)
03 . Multiple pregnancy is the most powerful predictive factor for
adverse maternal, obstetrical, and perinatal outcomes . Couples
should be thoroughly counselled about the significant risks
of multiple pregnancies associated with all assisted human
reproductive treatments . (II-2A)
04. The benefits and cumulative pregnancy rates of elective single
embryo transfer support a policy of using this protocol in couples
with good prognosis for success, and elective single embryo
transfer should be strongly encouraged in this population . (II-2A)
05 . To reduce the incidence of multiple pregnancy, health care
policies that support public funding for assisted human
reproduction, with regulations promoting best practice
regarding elective single embryo transfer, should be strongly
encouraged . (II-2A)
06 . Among singleton pregnancies, assisted reproductive technology
is associated with increased risks of preterm birth and low
birth weight infants, and ovulation induction is associated with
an increased risk of low birth weight infants. Until sufficient
research has clarified the independent roles of infertility and
treatment for infertility, couples should be counselled about the
risks associated with treatment . (II-2B) There is a role for closer
obstetric surveillance of women who conceive with assisted
human reproduction . (III-L)
07 . There is growing evidence that pregnancy outcomes are better
for cryopreserved embryos fertilized in vitro than for fresh embryo
transfers. This finding supports a policy of elective single embryo
transfer for women with a good prognosis (with subsequent use of
cryopreserved embryos as necessary), and may reassure women
who are considering in vitro fertilization . (II-2A)
08 . Women and couples considering assisted human reproduction
and concerned about perinatal outcomes in singleton pregnancies
should be advised that (1) intracytoplasmic sperm injection does
not appear to confer increased adverse perinatal or maternal risk
over standard in vitro fertilization, and (2) the use of donor oocytes
increases successful pregnancy rates in selected women, but even
when accounting for maternal age, can increase the risks of low
birth weight and preeclampsia . (II-2B)
09 . Any assisted reproductive technology procedure should be
prefaced by a discussion of fetal outcomes and the slight
increase in the risk of congenital structural abnormalities, with
emphasis on known confounding factors such as infertility and
body mass index . (II-2B)
10. In pregnancies achieved by artificial reproductive technology,
routine anatomic ultrasound for congenital structural abnormalities
is recommended between 18 and 22 weeks . (II-2A)
11 . Pregnancies conceived by intracytoplasmic sperm injection may
be at increased risk of chromosomal aberrations, including sex
chromosome abnormalities . Diagnostic testing should be offered
after appropriate counselling . (II-2A)
12 . The possible increased risk for late onset cancer due to gene
dysregulation for tumour suppression requires more long-term
follow-up before the true risk can be determined . (III-A)
13 . The clinical application of preimplantation genetic testing in
fertile couples must balance the benefits of avoiding disease
transmission with the medical risks and financial burden of in vitro
fertilization . (III-B)
14 . Preimplantation screening for aneuploidy is associated with
inconsistent findings for improving pregnancy outcomes. Any
discussion of preimplantation genetic screening with patients
should clarify that there is no adequate information on the long-
term effect of embryo single cell biopsy . (I-C)
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*Classification of recommendations†
I: Evidence obtained from at least one properly randomized
A . There is good evidence to recommend the clinical preventive action
II-1: Evidence from well-designed controlled trials without
B . There is fair evidence to recommend the clinical preventive action
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
C . The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
II-3: Evidence obtained from comparisons between times or
places with or without the intervention . Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
D . There is fair evidence to recommend against the clinical preventive action
E . There is good evidence to recommend against the clinical preventive
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care .176
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care .176
66 l JANUARY JOGC JANVIER 2014
SOGC CLINICAL PRACTICE GUIDELINES
fertility preservation after gonadotoxic treatments in
reproductive-age patients,4,5 to enable same-sex couples
and single women and men to conceive and have biological
children,6 and to facilitate the services of surrogate
gestational carriers.7 The ethical and philosophical issues
involved in AHR are complex and are handled differently in
different countries, resulting in varying levels of regulation
of these services.8–12
In Canada, the Assisted Human Reproduction Act,13
which covers topics including allowed (surrogacy, gamete
donation) and prohibited (human cloning, buying or selling
human reproductive material) processes, led to the creation
of Assisted Human Reproduction Canada, an agency
responsible for the licensing, monitoring, inspection, and
enforcement of regulations for ART clinics. Following a
2010 Supreme Court decision resulting from a Charter
challenge from Quebec, aspects of the Act relating to
prohibitions (sex selection, selling of human reproductive
material) have remained within the Federal Act, but much
of the regulation of ART services will fall back under
provincial jurisdiction.14 The 2012 Federal budget ordered
the dissolution of AHRC in 2013, with its responsibilities
redirected to Health Canada.4
Data for IVF clinics have been reported by the Canadian
Assisted Reproductive Technologies Registry since 1999,
under the auspices of the Canadian Fertility and Andrology
Society.15 IVF clinics are accredited by Accreditation
The availability of treatment for infertility and subfertility
(a term generally used to name any grade of reduced
fertility in couples unsuccessfully trying to conceive17) is
important to the family health of Canadians.18 Obstetrical
outcome data from pregnancies conceived by AHR and
some long-term follow-up data on offspring suggest
increased adverse outcomes related to AHR techniques.
Care providers and prospective parents should be aware
of these potential adverse outcomes.
This guideline reviews the outcome data of AHR pregnancies
using the Evaluation of Evidence criteria outlined in the
Report of the Canadian Task Force on the Periodic Health
Examination (Table 1). We searched the Cochrane Library
and Ovid MEDLINE for English-language articles related
to assisted reproduction and perinatal outcomes published
from February 2005 to December 2012 (overlapping with
the previous SOGC guideline). Well-conducted randomized
controlled trials were considered evidence of the highest
quality, followed by cohort studies. Key studies and
supporting data for each recommendation are referenced
and summarized with evaluative comments.
AHR assisted human reproduction
AHRC Assisted Human Reproduction Canada
aOR adjusted odds ratio
ART assisted reproductive technology
ASRM American Society for Reproductive Medicine
CARTR Canadian Assisted Reproductive Technologies Registry
CBAVD congenital bilateral absence of vas deferens
CFAS Canadian Fertility and Andrology Society
DET double embryo transfer
eSET elective single embryo transfer
ESHRE European Society of Human Reproduction and
ET embryo transfer
FET frozen embryo transfer
HFEA Human Fertilisation and Embryology Authority
HR hazard ratio
ISCI intracytoplasmic sperm injection
IUI intrauterine insemination
IVF in vitro fertilization
LBW low birth weight
MSAFP maternal serum alpha-fetoprotein
PAPP-A pregnancy-associated plasma protein-A
PGS preimplantation genetic screening
RR relative risk
OH ovarian hyperstimulation
OI ovulation induction
OS ovarian stimulation
SART Society for Assisted Reproduction Technologies
SGA small for gestational age
TTP time to pregnancy
that involves handling eggs, sperm, or both outside the
human body (in vitro). ART includes in vitro fertilization,
with or without intracytoplasmic sperm injection, with
fresh or frozen embryos (by cryopreservation or by
vitrification and thawed embryo transfer) and IVF with
donor oocytes, gamete intrafallopian transfer, zygote
intrafallopian transfer, and assisted zona hatching. ART
has expanded to include not only in vitro procedures, but
also intrauterine insemination and OS with gonadotropin
or ovarian stimulating medications1
lthough the definition varies, assisted reproductive
technology is commonly defined as any procedure
ART accounts for 1.7% to 4% of pregnancies2 and has
traditionally been used to address primary or secondary
infertility.3 More recently, its use has expanded to allow
JANUARY JOGC JANVIER 2014 l 81
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